Abstract P3-05-12: A matched cohort study of the prognosis of early breast cancer in patients with Li-Fraumeni syndrome
Authors: Vanessa Petry, Renata Colombo Bonadio, Daniela Jafet, Roberta Campos, Luiz Senna, Allyne Cagnacci, Laura Testa, Maria Candida Villares Fragoso, Maria del Pilar Estevez Diz
Journal: Cancer Research (2023)

Abstract Background: Patients with germline TP53 pathogenic variants (Li-Fraumeni syndrome - LFS) have an increased risk of breast cancer, which is the most common type of cancer in premenopausal women with LFS. These women are also at risk of other second malignancies, including radiotherapy-induced malignancies. On the other hand, little is known about the prognosis of breast cancer in patients with LFS or if the disease behavior differs from non-hereditary BC. The objective of this study was to characterize the phenotype and prognosis of early BC in patients with LFS compared to a matched cohort of patients without germline pathogenic variants (PV) related to BC. Methods: This retrospective study evaluated patients with early BC treated in an academic cancer center from Dec 1999 to Mar 2022. The LFS cohort included consecutive patients with BC who harbored a PV or likely PV of TP53. The matched control cohort (2:1) included patients with BC with no germline PV in a panel test. Primary endpoint was disease-free survival (DFS). Since LFS is associated with an increased risk of new primary malignancies, only locoregional and distant BC recurrence were considered as events in the DFS analysis. Secondary endpoints included response to systemic therapy, sites of recurrence, and breast cancer-related deaths. Results: Forty-six patients with LFS were evaluated; the control cohort included 91 matched patients. In the LFS cohort, 14 different PV or likely PV were identified, with TP53 p.R337H being the most common (n=32). Median age was 40 years in both groups. In the LFS cohort, 35% of the pts had HER2-positive BC compared to 21% in the control cohort. Primary tumors greater than 5 cm were observed in 15% of pts in the LFS cohort and 25% of pts in the control cohort. Positive lymph nodes were observed in 11% and 14%, respectively. Among 15 pts with LFS who received neoadjuvant chemotherapy, all (100%) had a response, with 5 (33%) complete responses. Thirty-five patients in the control group received neoadjuvant chemotherapy: 83% responded, with 11 (31%) presenting a complete response. With a median follow-up of 43 months, 5-year DFS rates were 82.6% (95% CI 65.1 – 91.9%) in the LFS cohort and 91.5% (95% CI 79.1 – 96.6%) in the control cohort (P=0.427). Rates and sites of recurrence, new primary BC, and deaths are detailed in the table. Conclusions: In addition to a higher risk of new primary breast cancer, LFS patients with early breast cancer had numerically higher rates of locoregional and distant recurrence in comparison with a matched cohort. Nevertheless, further studies are required to understand if these differences are due to tumor behavior particularities or to differences in therapeutic management. Recurrence and death events Citation Format: Vanessa Petry, Renata Colombo Bonadio, Daniela Jafet, Roberta Campos, Luiz Senna, Allyne Cagnacci, Laura Testa, Maria Candida Villares Fragoso, Maria del Pilar Estevez Diz. A matched cohort study of the prognosis of early breast cancer in patients with Li-Fraumeni syndrome [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-12.